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REVIEW

The molecular epidemiology of Treponema pallidum subspecies pallidum

Daphne Y. Ma A D , Lorenzo Giacani A B and Arturo Centurión-Lara C E
+ Author Affiliations
- Author Affiliations

A University of Washington, Department of Global Health, 325 9th Avenue, Seattle, WA, 98104, USA.

B University of Washington, Division of Allergy and Infectious Diseases, 325 9th Avenue, Seattle, WA, 98104, USA.

C Universidad Peruana Cayetano Heredia, Facultad de Salud Pública, Avenida Honorio Delgado 430, San Martín de Porres 15102, Lima, Perú.

D Present address: Emory University, Department of Pediatrics, Yerkes Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, USA.

E Corresponding author. Email: acentur@uw.edu

Sexual Health 12(2) 141-147 https://doi.org/10.1071/SH14197
Submitted: 14 October 2014  Accepted: 18 January 2015   Published: 7 April 2015

Abstract

Pathogens adapt and evolve in response to pressures exerted by host environments, leading to generation of genetically diverse variants. Treponema pallidum subspecies pallidum displays a substantial amount of interstrain diversity. These variants have been identified in various parts of the world, indicating transmission linkage between geographical regions. Genotyping is based on molecular characterisation of various loci in the syphilis treponeme genome, but still require further development and continued research, as new bacterial types are continually being detected. The goal for studying the molecular epidemiology of Treponema pallidum variants is the global monitoring of the transmission of genetically distinct organisms with different drug sensitivities and, potentially, different virulence proprieties.


References

[1]  Gerbase AC, Rowley JT, Heymann DH, Berkley SF, Piot P. Global prevalence and incidence estimates of selected curable STDs. Sex Transm Infect 1998; 74 S12–6.
| 10023347PubMed |

[2]  Centers for Disease Control and Prevention. Primary and secondary syphilis - United States, 2000–2001. MMWR Morb Mortal Wkly Rep 2002;; 51 971–3.
| 12433021PubMed |

[3]  Sasse A, Defraye A, Ducoffre G. Recent syphilis trends in Belgium and enhancement of STI surveillance systems. Euro Surveill 2004; 9 6–8.
| 1:STN:280:DC%2BD2MrhvVGrsg%3D%3D&md5=f7c06742827a3cd6b9d9f6a6b47f41d1CAS | 15677856PubMed |

[4]  Righarts AA, Simms I, Wallace L, Solomou M, Fenton KA. Syphilis surveillance and epidemiology in the United Kingdom. Euro Surveill 2004; 9 21–5.
| 1:STN:280:DC%2BD2MrhvVGktA%3D%3D&md5=9ff868f50e1272a1f06dddbe7d51e400CAS | 15677851PubMed |

[5]  Marcus U, Bremer V, Hamouda O. Syphilis surveillance and trends of the syphilis epidemic in Germany since the mid-90s. Euro Surveill 2004; 9 11–4.
| 1:STN:280:DC%2BD2MrhvVGkug%3D%3D&md5=25d8bc88239be36bee7b2da1782b1ab8CAS | 15677854PubMed |

[6]  Nichols HJ. Observations on a strain of Spirochaeta pallida isolated from the nervous system. J Exp Med 1914; 19 362–71.
Observations on a strain of Spirochaeta pallida isolated from the nervous system.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3crjsVClsw%3D%3D&md5=c72525aa68f90cdbec2d2a9e8552db43CAS | 19867775PubMed |

[7]  Pillay A, Liu H, Chen CY, Holloway B, Sturm AW, Steiner B, et al Molecular subtyping of Treponema pallidum subspecies pallidum. Sex Transm Dis 1998; 25 408–14.
Molecular subtyping of Treponema pallidum subspecies pallidum.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1cvks1Kjuw%3D%3D&md5=dc0431c5c5b15ea91a9b6b65c8fb696bCAS | 9773432PubMed |

[8]  Marra C, Sahi S, Tantalo L, Godornes C, Reid T, Behets F, et al Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 2010; 202 1380–8.
Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFSnsbjO&md5=7c35267caf854f62e6bccca0b6ea222eCAS | 20868271PubMed |

[9]  Pope V, Fox K, Liu H, Marfin AA, Leone P, Sena AC, Chapin J, Fears MB, Markowitz L. Molecular subtyping of Treponema pallidum from North and South Carolina. J Clin Microbiol 2005; 43 3743–6.
Molecular subtyping of Treponema pallidum from North and South Carolina.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXpvVCrtLw%3D&md5=906cd949599d306a001020abdd6432c9CAS | 16081904PubMed |

[10]  Sutton MY, Liu H, Steiner B, Pillay A, Mickey T, Finelli L, Morse S, Markowitz LE, St Louis ME. Molecular subtyping of Treponema pallidum in an Arizona County with increasing syphilis morbidity: use of specimens from ulcers and blood. J Infect Dis 2001; 183 1601–6.
Molecular subtyping of Treponema pallidum in an Arizona County with increasing syphilis morbidity: use of specimens from ulcers and blood.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktl2ksbg%3D&md5=ef3d0bc43ee4ba8d84fb4ebc50a08c75CAS | 11343208PubMed |

[11]  Cole MJ, Chisholm SA, Palmer HM, Wallace LA, Ison CA. Molecular epidemiology of syphilis in Scotland. Sex Transm Infect 2009; 85 447–51.
Molecular epidemiology of syphilis in Scotland.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1Mnos12jug%3D%3D&md5=366ccc61a2938e159a4ab06a31a63ed0CAS | 19497918PubMed |

[12]  Martin IEGW, Yang Y. Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai, China. Clin Infect Dis 2009; 49 515–21.
Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai, China.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVOmsr%2FI&md5=8083995871280876c4b20f00c02d2ebfCAS |

[13]  Molepo J, Pillay A, Weber B, Morse SA, Hoosen AA. Molecular typing of Treponema pallidum strains from patients with neurosyphilis in Pretoria, South Africa. Sex Transm Infect 2007; 83 189–92.
| 1:STN:280:DC%2BD2szlsFSrsQ%3D%3D&md5=6803882b059661fd2d7547fc634dd33eCAS | 17244664PubMed |

[14]  Florindo C, Reigado V, Gomes JP, Azevedo J, Santo I, Borrego MJ. Molecular typing of Treponema pallidum clinical strains from Lisbon, Portugal. J Clin Microbiol 2008; 46 3802–3.
Molecular typing of Treponema pallidum clinical strains from Lisbon, Portugal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1cjgslantg%3D%3D&md5=c719392e67265f418e308b85d62d56eeCAS | 18753355PubMed |

[15]  Ho EL, Lukehart SA. Syphilis: using modern approaches to understand an old disease. J Clin Invest 2011; 121 4584–92.
Syphilis: using modern approaches to understand an old disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1ShsLrM&md5=98bb607d550e336feaaaff265695d4d3CAS | 22133883PubMed |

[16]  Sutton MY, Liu H, Steiner B, Pillay A, Mickey T, Finelli L, Morse S, Markowitz LE, St Louis ME. Molecular subtyping of Treponema pallidum in an Arizon County with increasing syphilis morbidity: use of specimens from ulcers and blood. J Infect Dis 2001; 183 1601–6.
Molecular subtyping of Treponema pallidum in an Arizon County with increasing syphilis morbidity: use of specimens from ulcers and blood.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktl2ksbg%3D&md5=ef3d0bc43ee4ba8d84fb4ebc50a08c75CAS | 11343208PubMed |

[17]  Mikalová L, Pospisilova P, Woznicova V, Kuklova I, Zakoucka H, Smajs D. Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient. BMC Microbiol 2013; 13 178
Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient.Crossref | GoogleScholarGoogle Scholar | 23898829PubMed |

[18]  Gerbase AC, Rowley JT, Heymann DH, Berkley SF, Piot P. Global prevalence and incidence estimates of selected curable STDs. Sex Transm Infect 1998; 74 12–6.

[19]  Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, et al Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 1998; 281 375–88.
Complete genome sequence of Treponema pallidum, the syphilis spirochete.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXkslaguro%3D&md5=04d6c9f08e41bd2f450c42f9f7a65478CAS | 9665876PubMed |

[20]  Petrosova H, Zobanikova M, Cejkova D, Mikalova L, Pospisilova P, Strouhal M, et al Whole genome sequence of Treponema pallidum ssp. pallidum, strain Mexico A, suggests recombination between yaws and syphilis strains. PLoS Negl Trop Dis 2012; 6 e1832
Whole genome sequence of Treponema pallidum ssp. pallidum, strain Mexico A, suggests recombination between yaws and syphilis strains.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsVaktrvL&md5=5614c013cf1e0e7f72c0b1140684484bCAS | 23029591PubMed |

[21]  Giacani L, Iverson-Cabral SL, King JC, Molini BJ, Lukehart SA, Centurion-Lara A. Complete genome sequence of the Treponema pallidum subsp. pallidum Sea81–4 Strain. Genome Announc 2014; 2 e00333-14
Complete genome sequence of the Treponema pallidum subsp. pallidum Sea81–4 Strain.Crossref | GoogleScholarGoogle Scholar | 24744342PubMed |

[22]  Matejkova P, Strouhal M, Smajs D, Norris SJ, Palzkill T, Petrosino JF, et al Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays. BMC Microbiol 2008; 8 76
Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays.Crossref | GoogleScholarGoogle Scholar | 18482458PubMed |

[23]  Zobanikova M, Mikolka P, Cejkova D, Pospisilova P, Chen L, Strouhal M, et al Complete genome sequence of Treponema pallidum strain DAL-1. Stand Genomic Sci 2012; 7 12–21.
Complete genome sequence of Treponema pallidum strain DAL-1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs1yrurrP&md5=9a76996acc4fdb999830222d6c5485caCAS | 23449808PubMed |

[24]  Giacani L, Jeffrey BM, Molini BJ, Le HT, Lukehart SA, Centurion-Lara A, et al Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain. J Bacteriol 2010; 192 2645–6.
Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXms1emsr0%3D&md5=261972ab78033dec6a04754dbe321579CAS | 20348263PubMed |

[25]  Stamm LV, Kerner TC, Bankaitis VA, Bassford PJ. Identification and preliminary characterization of Treponema pallidum protein antigens expressed in Escherichia coli. Infect Immun 1983; 41 709–21.
| 1:CAS:528:DyaL3sXkvVKhurw%3D&md5=fc0b253a21932dfa1048967aa909c444CAS | 6347894PubMed |

[26]  Petrosova H, Pospisilova P, Strouhal M, Cejkova D, Zobanikova M, Mikalova L, et al Resequencing of Treponema pallidum ssp. pallidum strains Nichols and SS14: correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters. PLoS ONE 2013; 8 e74319
Resequencing of Treponema pallidum ssp. pallidum strains Nichols and SS14: correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVyrsLbL&md5=40d86040fce4fb2d1a51f2783c428916CAS | 24058545PubMed |

[27]  Stamm LV, Bergen HL. A point mutation associated with bacterial macrolide resistance is present in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate. Antimicrob Agents Chemother 2000; 44 806–7.
A point mutation associated with bacterial macrolide resistance is present in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhsVGgsLg%3D&md5=8cc7c013da0a5f81b05ba6d008af1a93CAS | 10755994PubMed |

[28]  Nechvatal L, Petrosova H, Grillova L, Pospisilova P, Mikalova L, Strnadel R, et al Syphilis-causing strains belong to separate SS14-like or Nichols-like groups as defined by multilocus analysis of 19 Treponema pallidum strains. Int J Medical Microbiology 2014; 304 645–53.
Syphilis-causing strains belong to separate SS14-like or Nichols-like groups as defined by multilocus analysis of 19 Treponema pallidum strains.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXosFant7g%3D&md5=efb30dfc42c8e197a25fde2fe28764a2CAS |

[29]  Mikalova L, Strouhal M, Cejkova D, Zobanikova M, Pospisilova P, Norris SJ, et al Genome analysis of Treponema pallidum subsp. pallidum and subsp. pertenue strains: most of the genetic differences are localized in six regions. PLoS ONE 2010; 5 e15713
Genome analysis of Treponema pallidum subsp. pallidum and subsp. pertenue strains: most of the genetic differences are localized in six regions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXltVamtg%3D%3D&md5=5c5c0981307f62f94957ce0bbe7de3ccCAS | 21209953PubMed |

[30]  Giacani L, Chattopadhyay S, Centurion-Lara A, Jeffrey BM, Le HT, Molini BJ, et al Footprint of positive selection in Treponema pallidum subsp. pallidum genome sequences suggests adaptive microevolution of the syphilis pathogen. PLoS Negl Trop Dis 2012; 6 e1698
Footprint of positive selection in Treponema pallidum subsp. pallidum genome sequences suggests adaptive microevolution of the syphilis pathogen.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XpsVygurc%3D&md5=7632c169a4bd91d3957595d9501e56ceCAS | 22720110PubMed |

[31]  Harper KN, Ocampo PS, Steiner BM, George RW, Silverman MS, Bolotin S, et al On the origin of the treponematoses: a phylogenetic approach. PLoS Negl Trop Dis 2008; 2 e148
On the origin of the treponematoses: a phylogenetic approach.Crossref | GoogleScholarGoogle Scholar | 18235852PubMed |

[32]  Wendel GD, Sanchez PJ, Peters MT, Harstad TW, Potter LL, Norgard MV. Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies complicated by congenital syphilis. Obstet Gynecol 1991; 78 890–5.
| 1923218PubMed |

[33]  Centurion-Lara A, Giacani L, Godomes C, Molini BJ, Brinck Reid T, Lukehart SA. Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. PLoS Negl Trop Dis 2013; 7 e2222
Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXpvVKmtr4%3D&md5=7c685f00142096f32b3c057300a42941CAS | 23696912PubMed |

[34]  Peng RR, Wang AL, Li J, Tucker JD, Yin YP, Chen XS. Molecular typing of Treponema pallidum: a systematic review and meta-analysis. PLoS Negl Trop Dis 2011; 5 e1273
Molecular typing of Treponema pallidum: a systematic review and meta-analysis.Crossref | GoogleScholarGoogle Scholar | 22087340PubMed |

[35]  Maiden MC. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci USA 1998; 95 3140–5.
Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXitV2itLg%3D&md5=5d7e3de45795cffea8e7682cb274d792CAS | 9501229PubMed |

[36]  Spratt BG, Maiden MC. Bacterial population genetics, evolution and epidemiology. Philos Trans R Soc Lond B Biol Sci 1999; 354 701–10.
Bacterial population genetics, evolution and epidemiology.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M3ptlOgsg%3D%3D&md5=a7512c23ec48950167d3b6c869133e92CAS | 10365396PubMed |

[37]  Franceschi F, Kanyo Z, Sherer EC, Sutcliffe J. Macrolide resistance from the ribosome perspective. Curr Drug Targets Infect Disord 2004; 4 177–91.
Macrolide resistance from the ribosome perspective.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnslCmsL8%3D&md5=6609ff15d8489c2000eb532d7889ea4fCAS | 15379729PubMed |

[38]  Katz KA, Klausner JD. Azithromycin resistance in Treponema pallidum. Curr Opin Infect Dis 2008; 21 83–91.
Azithromycin resistance in Treponema pallidum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsVajsQ%3D%3D&md5=76de2b8eb122603e5908d00ed3832988CAS | 18192791PubMed |

[39]  Stamm LV. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother 2010; 54 583–9.
Global challenge of antibiotic-resistant Treponema pallidum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhvFSitLs%3D&md5=489f40435f792fccc45bc4e87ecd213bCAS | 19805553PubMed |

[40]  Lukehart SA, Godomes C, Molini BJ, Sonnett P, Hopkins S, Mulcahy F, Engelman J, Mitchell SJ, Rompalo AM, Marra CM, Klausner JD. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 2004; 351 154–8.
Macrolide resistance in Treponema pallidum in the United States and Ireland.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXls1elsbo%3D&md5=3604d7e41d40657a192a467d71d2d893CAS | 15247355PubMed |

[41]  Marra CM, Colina AP, Godornes C, Tantalo LC, Puray M, Centurion-Lara A, Lukehart SA. Antibiotic selection may contribute to increases in macrolide resistant Treponema pallidum. J Infect Dis 2006; 194 1771–3.
Antibiotic selection may contribute to increases in macrolide resistant Treponema pallidum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhvVKltA%3D%3D&md5=f86a8deb8b6fff74ced4eee2b50525dcCAS | 17109351PubMed |

[42]  Matejkova P, Flasarova M, Zakoucka H, Borek M, Kremenova S, Arenberger P, et al Macrolide treatment failure in a case of secondary syphilis: a novel A2059G mutation in the 23S rRNA gene of Treponema pallidum subsp. pallidum. J Med Microbiol 2009; 58 832–6.
Macrolide treatment failure in a case of secondary syphilis: a novel A2059G mutation in the 23S rRNA gene of Treponema pallidum subsp. pallidum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnsF2nu7Y%3D&md5=0adba52b208cffd8f882d4b44bc484deCAS | 19429763PubMed |

[43]  Riedner G, Rusizokla M, Todd J, Maboko L, Hoelscher M, Mmbando D, Samky E, Lyamuya E, Mabey D, Grosskurth H, Hayes R. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med 2005; 353 1236–44.
Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVeltL%2FF&md5=95f294d5e90bbfaa39412a06b508128eCAS | 16177249PubMed |

[44]  Kiddugavu MK, Kiwanuka N, Wawer MJ, Serwadda D, Sewankambo NK, Wabwire-Mangen F, Makumbi F, Li X, Reynolds SJ, Quinn TC, The Rakai Study Group, Kiddugavu MK, Kiwanuka N, Wawer MJ, Serwadda D, Sewankambo NK, Wabwire-Mangen F, Makumbi F, Li X, Reynolds SJ, Quinn TC, The Rakai Study Group, Effectiveness of syphilis treatment using azithromycin and/or benzathine penicillin in Rakai, Uganda. Sex Transm Dis 2005; 32 1–6.
Effectiveness of syphilis treatment using azithromycin and/or benzathine penicillin in Rakai, Uganda.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtFeju7zF&md5=2e767b65a65873fe0ecb0f93299ecc6bCAS |

[45]  Hook EW, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC, Martin D, Langley C, McNeil L, Wolff M. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010; 201 1729–35.
A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXnvFKitb0%3D&md5=617325e215beed36f78de1ef0d15eda9CAS | 20402591PubMed |

[46]  Centers for Disease Control and Prevention Azithromycin treatment failures in syphilis infections–San Francisco, California, 2002–2003. MMWR Morb Mortal Wkly Rep 2004; 53 197–8.
| 15017376PubMed |

[47]  Chen JC. Update on emerging infections: news from the Centers for Disease Control and Prevention. Brief report: azithromycin treatment failures in syphilis infections–San Francisco, California, 2002–2003. Ann Emerg Med 2004; 44 232–3.
Update on emerging infections: news from the Centers for Disease Control and Prevention. Brief report: azithromycin treatment failures in syphilis infections–San Francisco, California, 2002–2003.Crossref | GoogleScholarGoogle Scholar | 15332064PubMed |

[48]  Mitchell SJ, Engelman J, Kent CK, Lukehart SA, Godornes C, Klausner JD. Azithromycin-resistant syphilis infection: San Francisco, California, 2000–2004. Clin Infect Dis 2006; 42 337–45.
Azithromycin-resistant syphilis infection: San Francisco, California, 2000–2004.Crossref | GoogleScholarGoogle Scholar | 16392078PubMed |

[49]  Klausner JD, Kohn RP, Kent CK. Azithromycin versus penicillin for early syphilis. N Engl J Med 2006; 354 203–5, author reply 203–5.
Azithromycin versus penicillin for early syphilis.Crossref | GoogleScholarGoogle Scholar | 16411292PubMed |

[50]  Grillova L, Petrosova H, Mikalova L, Strnadel R, Dastychova E, Kuklova I, et al Molecular typing of Treponema pallidum in the Czech Republic during 2011 to 2013: increased prevalence of identified genotypes and of isolates with macrolide resistance. J Clin Microbiol 2014; 52 3693–700.
Molecular typing of Treponema pallidum in the Czech Republic during 2011 to 2013: increased prevalence of identified genotypes and of isolates with macrolide resistance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhvF2qurbL&md5=b333b05b501a4a6e505db9a5b8fcb134CAS | 25100820PubMed |

[51]  Flasarova M, Pospisilova P, Mikalova L, Valisova Z, Dastychova E, Strnadel R, et al Sequencing-based molecular typing of Treponema pallidum strains in the Czech Republic: all identified genotypes are related to the sequence of the SS14 strain. Acta Derm Venereol 2012; 92 669–74.
Sequencing-based molecular typing of Treponema pallidum strains in the Czech Republic: all identified genotypes are related to the sequence of the SS14 strain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs12nt7fN&md5=19dd0c5bb4d38ead05e619cf3f60cceeCAS | 22434073PubMed |

[52]  Tipple C, McClure MO, Taylor GP. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Sex Transm Infect 2011; 87 486–8.
High prevalence of macrolide resistant Treponema pallidum strains in a London centre.Crossref | GoogleScholarGoogle Scholar | 21917695PubMed |

[53]  Read P, Jeoffreys N, Tagg K, Guy RJ, Gilbert GL, Donovan B. Azithromycin-resistant syphilis-causing strains in Sydney, Australia: prevalence and risk factors. J Clin Microbiol 2014; 52 2776–81.
Azithromycin-resistant syphilis-causing strains in Sydney, Australia: prevalence and risk factors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhs12ltbbL&md5=113acf851380a1f90f515f1a7115341cCAS | 24850356PubMed |

[54]  Su JR, Pillay A, Hook EW, Ghanem KG, Wong W, Jackson D, Smith LD, Pierce E, Philip SS, Wilson S, Golden MR, Workowski KA, Chi KH, Parrish DD, Chen CY, Weinstock HS. Prevalence of the 23S rRNA A2058G point mutation and molecular subtypes in Treponema pallidum in the United States, 2007 to 2009. Sex Transm Dis 2012; 39 794–8.

[55]  Marra CM, Colina AP, Godornes C, Tantalo LC, Puray M, Centurion-Lara A, et al Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum. J Infect Dis 2006; 194 1771–3.
Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhvVKltA%3D%3D&md5=f86a8deb8b6fff74ced4eee2b50525dcCAS | 17109351PubMed |

[56]  Wu BR, Yang CJ, Tsai MS, Lee KY, Lee NY, Huang WC, et al Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009–2013. Clin Micro Infect 2014; 20 802–7.
Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009–2013.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsValsbjN&md5=7f3d090139c0a294c1eef5a2f166127bCAS |